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Recovery of Proteins from States of Extreme Dehydration

Percent change in the volume of the model crystal’s unit cell as water adsorbs from a humid vapor phase.

More than half of biological pharmaceuticals are stored as freeze-dried powders to prevent aggregation and degradation processes that can occur during long-term storage in aqueous environments.  In an ongoing effort to understand why many biologics exhibit reduced therapeutic efficacy when they are rehydrated from freeze-dried powders, we have developed a novel computational technique to simulate water sorption on proteins. In the first application of this new method (J. Phys. Chem. Lett., 3, 2942, 2012), we examined water sorption on a model ubiquitin crystal (left) and observed computationally that protein structure and dynamics change dramatically during rehydration.  One notable structural change is the volumetric swelling that protein systems exhibit in response to water uptake.  This effect is illustrated in the image at the top, which shows the percent change in the volume of the model crystal’s unit cell as water adsorbs from a humid vapor phase. The relative humidity of the vapor phase is shown on the x-axis, and the insets are renderings of the crystal illustrating the progression of the rehydration process.  These results are in quantitative agreement with optical and X-ray measurements taken on real protein systems.

For more infomation about Professor Debenedetti's research please see the Debenedetti Research Group site.